Persistent oxygen-glucose deprivation induces astrocytic death through two different pathways and calpain-mediated proteolysis of cytoskeletal proteins during astrocytic oncosis

Xu, Chang; Zhang, Ying; Zou, Lina; Xiao, Heng; Chu, Yinghao; Chu, Xun

doi:10.1016/j.neulet.2010.05.040

Cited by 25 publications

(18 citation statements)

References 29 publications

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“…4 Oncosis generally occurs in seconds to minutes at most 1 h and the lysis of cells can be observed in short time. 9,10,19 Our dynamic observation that taxol does not induce the collapse of microtubules cytoskeleton after cytoplasm vacuolization (see Fig. 2) further demonstrated that taxolinduced cell death with cytoplasm vacuolization is not oncosis.…”

Section: Discussionsupporting

confidence: 55%

“…4 It is recognized that breakdown of the plasma membrane and downregulation of the cytoskeleton-associated proteins such as talin, paxillin and vinculin are associated with oncosis. 9 Loo et al 10 also demonstrated that RAV12 caused oncosis by inducing disruption of cytoskeleton. Moreover, in oncosis, cellular energy depletion following metabolic insults such as severe ischemia produces dramatic reduction in mitochondrial respiration and ATP synthesis, resulting in a loss of ionic homeostasis and cellular swelling.…”

Section: Introductionmentioning

confidence: 98%

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TAXOL INDUCES CELL DEATH WITH CYTOPLASM VACUOLIZATION IN PARAPTOSIS-LIKE BUT NOT ONCOSIS FASHION IN ASTC-a-1 CELLS

Quan

Wang

et al. 2013

J. Innov. Opt. Health Sci.

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Recently, we found that high concentration of taxol (70 M) induced cell death with cytoplasm vacuolization, the typical characteristic of both paraptosis and oncosis, in human lung carcinoma (ASTC-a-1) cells. This report was designed to further determine the form of taxol-induced cell death with cytoplasm vacuolization. It is generally considered that the cytoplasm vacuolization in oncosis due to the swelling of endoplasmic reticulum (ER), mitochondria, lysosomes and nuclei occurs after the loss of mitochondrial membrane potential (ÁÉm). However,°ow cytometry (FCM) analysis showed that taxol-induced cytoplasm vacuolization preceded the loss of ÁÉm. Moreover, taxol treatment did not induce the collapse of microtubule, the typical characteristic of oncosis. These data demonstrated that taxol-induced cell death with cytoplasm vacuolization is not oncosis. FCM analysis by Annexin V-FITC/PI apoptosis detection kit further demonstrated that taxol-induced cell death with cytoplasm vacuolization is not apoptosis. In conclusion, in combination with our recent in vitro and in vivo data, this report further demonstrates that high concentration of taxol induces cell death with cytoplasm vacuolization in paraptosis-like but not oncosis fashion.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 98%

TAXOL INDUCES CELL DEATH WITH CYTOPLASM VACUOLIZATION IN PARAPTOSIS-LIKE BUT NOT ONCOSIS FASHION IN ASTC-a-1 CELLS

Quan

Wang

et al. 2013

J. Innov. Opt. Health Sci.

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“…The intracellular ATP level of fluopsin C-treated MCF-7 cells at 3 h was depleted to less than 35% of the control, which confirmed that fluopsin C could induce oncosis in MCF-7 cells rather than apoptosis. Several investigators have shown that cells in an aerobic environment are constantly generating ROS [23,24] . Because the physiologic levels of ROS can serve as signaling molecules to regulate transcription, excessive ROS production leads to oxidative stress, damage to intracellular molecules and organelles, and, ultimately, cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Fluopsin C induced ATP depletion, ROS generation and Δψ m collapse Several studies have suggested that ROS and cellular ATP play a pivotal role in determining whether cell death is apoptotic or oncotic [2,23,24] . Figure 8A shows that the cellular ATP content of MCF-7 cells in the presence and absence of fluopsin C was significantly decreased.…”

Section: Fluopsin C Destroyed the Cell Skeletonmentioning

confidence: 99%

Fluopsin C induces oncosis of human breast adenocarcinoma cells

Jiang

Cui

et al. 2013

Acta Pharmacol Sin

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Aim: Fluopsin C, an antibiotic isolated from Pseudomonas jinanesis, has shown antitumor effects on several cancer cell lines. In the current study, the oncotic cell death induced by fluopsin C was investigated in human breast adenocarcinoma cells in vitro. Methods: Human breast adenocarcinoma cell lines MCF-7 and MD-MBA-231 were used. The cytotoxicity was evaluated using MTT assay. Time-lapse microscopy and transmission electron microscopy were used to observe the morphological changes. Cell membrane integrity was assessed with propidium iodide (PI) uptake and lactate dehydrogenase (LDH) assay. Flow cytometry was used to measure reactive oxygen species (ROS) level and mitochondrial membrane potential (Δψm). A multimode microplate reader was used to analyze the intracellular ATP level. The changes in cytoskeletal system were investigated with Western blotting and immunostaining.Results: Fluopsin C (0.5-8 μmol/L) reduced the cell viability in dose-and time-dependent manners. Its IC 50 values in MCF-7 and MD-MBA-231 cells at 24 h were 0.9 and 1.03 μmol/L, respectively. Fluopsin C (2 μmol/L) induced oncosis in both the breast adenocarcinoma cells characterized by membrane blebbing and swelling, which was blocked by pretreatment with the pan-caspase inhibitor Z-VAD-fmk. In MCF-7 cells, fluopsin C caused PI uptake into the cells, significantly increased LDH release, induced cytoskeletal system degradation and ROS accumulation, decreased the intracellular ATP level and Δψm. Noticeably, fluopsin C exerted comparable cytotoxicity against the normal human hepatocytes (HL7702) and human mammary epithelial cells with the IC 50 values at 24 h of 2.7 and 2.4 μmol/L, respectively. Conclusion: Oncotic cell death was involved in the anticancer effects of fluopsin C on human breast adenocarcinoma cells in vitro. The hepatoxicity of fluopsin C should not be ignored.

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“…However, a growing body of evidence suggests that astrocytes located in the ischaemic core undergo another important death pathway termed oncosis [6,9,[12][13][14] . Intracellular energy storage is the key factor that decides the specific cell death pathways of damaged brain cells [13,15,16] , and it shows the dynamic changes as injury time goes on. The dual role that PARP-1 plays in cerebral ischemia-reperfusion depends on the intracellular energy storage and injury severity.…”

mentioning

confidence: 99%

Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways

Cai

Zhang

Huang

et al. 2015

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Poly (ADP-ribose) polymerase-1 (PARP-1) plays as a double edged sword in cerebral ischemia-reperfusion, hinging on its effect on the intracellular energy storage and injury severity, and the prognosis has relationship with intervention timing. During ischemia injury, apoptosis and oncosis are the two main cell death pathway sin the ischemic core. The participation of astrocytes in ischemia-reperfusion induced cell death has triggered more and more attention. Here, we examined the protective effects and intervention timing of the PARP-1 inhibitor PJ34, by using a mixed oxygen-glucose deprivation/reperfusion (OGDR) model of primary rat astrocytes in vitro, which could mimic the ischemia-reperfusion damage in the "ischemic core". Meanwhile, cell death pathways of various PJ34 treated astrocytes were also investigated. Our results showed that PJ34 incubation (10 μmol/L) did not affect release of lactate dehydrogenase (LDH) from astrocytes and cell viability or survival 1 h after OGDR. Interestingly, after 3 or 5 h OGDR, PJ34 significantly reduced LDH release and percentage of PI-positive cells and increased cell viability, and simultaneously increased the caspase-dependent apoptotic rate. The intervention timing study demonstrated that an earlier and longer PJ34 intervention during reperfusion was associated with more apparent protective effects. In conclusion, earlier and longer PJ34 intervention provides remarkable protective effects for astrocytes in the "ischaemic core" mainly by reducing oncosis of the astrocytes, especially following serious OGDR damage.

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Persistent oxygen-glucose deprivation induces astrocytic death through two different pathways and calpain-mediated proteolysis of cytoskeletal proteins during astrocytic oncosis

Cited by 25 publications

References 29 publications

TAXOL INDUCES CELL DEATH WITH CYTOPLASM VACUOLIZATION IN PARAPTOSIS-LIKE BUT NOT ONCOSIS FASHION IN ASTC-a-1 CELLS

TAXOL INDUCES CELL DEATH WITH CYTOPLASM VACUOLIZATION IN PARAPTOSIS-LIKE BUT NOT ONCOSIS FASHION IN ASTC-a-1 CELLS

Fluopsin C induces oncosis of human breast adenocarcinoma cells

Intervention timing and effect of PJ34 on astrocytes during oxygen-glucose deprivation/reperfusion and cell death pathways

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